Organic compounds which can bind selectively at the active centers of proteins and then react to give an irreversibly modified protein are potentially important chemotherapeutic agents. Such materials for the modification of alpha-chymotrypsin (and other serine proteases) and serum albumin are under study. These reagents contain fluorine substituents or, in a few cases, positions enriched in carbon-13. High-resolution and pulsed nmr investigations of these nuclei at the protein binding site can potentially identify the reactive functional groups near this site. Also of interest is how the nature of the binding site changes with variables such as temperature and pH. It is hoped that this work will lead to generally applicable techniques for characterizing the chemical nature of a given binding site and thereby facilitate the development of binding site-directed chemotherapeutic agents. BIBLIOGRAPHIC REFERENCE: Conformations of Glycyl-trans-4-fluoro-L-prolyl-L-tryptophan in Aqueous Solution, J.T. Gerig and R.S. McLeod, J. Amer. Chem. Soc., 98, 3970 (1976).